Effect of Aviptadil, a Novel Therapy, on Clinical Outcomes of Patients with Viral-related Severe ARDS: A Retrospective Observational Study.

Background: Dealing with life-threatening viral acute respiratory distress syndrome (ARDS) has always been challenging and with the recent COVID pandemic experience, there is still the need of newer therapies to alleviate mortality. Aviptadil, has shown significant beneficial results in covid. We share our experience with this molecule by doing a retrospective study to evaluate the effect of this drug on clinical outcomes in viral-related Ards patients. Materials and methods: In this study, all patients with severe viral-related Ards received Aviptadil along with the conventional treatment. The oxygen saturation, SpO2/FiO2 (ratio of pulse oximetric saturation to fractional inspired oxygen) (S/F) ratio and PaO2/FiO2 (ratio of arterial oxygen partial pressure to fractional inspired oxygen) (p/f) ratio, before and after completion of the drug were studied. Radiological clearance and time for complete recovery from respiratory failure was noted. All variables pre- and postadministration of the drug were compared. Results: A total of 68 patients with viral pneumonias were admitted to intensive care unit (Icu) and only 6 patients had severe Ards, who received Aviptadil. The mean oxygen saturation significantly improved from 87.86% before the first Aviptadil dose to 93.43% post 3 days of infusion. Similarly, improvement was seen in PaO2 values from 54.32 to 68.4 posttherapy (p-value < 0.004). SpO2/FiO2 (ratio of pulse oximetric saturation to fractional inspired oxygen) ratio hiked from 149 to 336 at the end of the 3 days infusion (p-value < 0.003). RALE scoring system was used for radiological clearance and the mean change in the score was from 6.42 to 2.5 (p-value 0.00). The average length of stay in the Icu was 12.14 days. No adverse effects were noted. Conclusion: Aviptadil has shown to improve the clinical outcomes in patients with severe viral-related ards without any adverse effects. How to cite this article: Sampley S, Bhasin D, Sekhri K, Singh H, Gupta O. Effect of Aviptadil, a Novel Therapy, on Clinical Outcomes of Patients with Viral-related Severe ARDS: A Retrospective Observational Study. Indian J Crit Care Med 2024;28(1):70-74.

Cerebral Aspergillosis Complicating COVID Recovery.

How to cite this article: Sampley S, Bhasin D, Singh H, Mishra S. Cerebral Aspergillosis Complicating COVID Recovery. Indian J Crit Care Med 2022;26(4):535-536.

Plasmapheresis for Pulmonary Hemorrhage Following Viperine Snakebite: A Case Report with Review of Literature.

INTRODUCTION: Snakebites are one of the commonest occupational hazards in tropical countries and viperine bites are potential to cause systemic toxicity. Coagulopathies and acute kidney injury (AKI) have been documented and easily dealt with in past, but pulmonary hemorrhage has been rarely seen and plasmapheresis has shown promising result for the same. This case reports highlight the effective use of plasmapheresis for pulmonary hemorrhage post-snakebite. BACKGROUND: Viperine snakebite has been associated with high morbidity and mortality due to its toxic systemic envenomization. The important systemic manifestations are coagulopathy, neuromuscular paralysis, AKI, myotoxicity, and cardiovascular collapse. Antivenomization, renal replacement therapy, steroids, and other supportive care are considered to be the mainstay of treatment till date. Pulmonary hemorrhage has been an unusual manifestation of viper bite and rarely reported and steroids have been used in such scenario but with mixed results. Role of plasmapheresis has been documented in the management of snakebite but especially for hematological problems and in limb preservation/salvage strategies. The use of same, for pulmonary hemorrhage has not been studied yet. Here, we present a rare case of pulmonary hemorrhage along with renal failure following viper bite which was successfully treated with plasmapheresis. To the best of our knowledge, it is a rare presentation and has not been reported in the literature reviewed till date. CASE DESCRIPTION: A previously healthy, 36-year-old man presented to our hospital 48 hours after a viper bite. He developed local as well systemic manifestations evident as hemolysis and renal failure. Gradually, he started having hemoptysis followed by respiratory failure requiring ventilatory support. CT chest done was s/o bilateral pulmonary hemorrhages correlating clinically with ongoing tracheal bleed. He had no other bleeding manifestations and had normal coagulation profile. He was initially treated with methylprednisolone therapy, but then did not show any improvement and finally plasmapheresis was done as rescue therapy. Following this, he had improvement in respiratory parameters and settling tracheal bleed with resolution of radiological changes. He was successfully weaned off from the ventilation and also his renal failure also improved with near normalization of pulmonary and renal functions. CONCLUSION: This case highlights the unusual presentation of pulmonary hemorrhage in a patient with viperine bite with normal coagulation and was aggressively managed with plasmapheresis. Hence, plasmapheresis can be used as life-saving modality in patients with systemic envenomization post-viperine bit. HOW TO CITE THIS ARTICLE: Sampley S, Sakhuja V, Bhasin D, Singh K, Singh H. Plasmapheresis for Pulmonary Hemorrhage Following Viperine Snakebite: A Case Report with Review of Literature. Indian J Crit Care Med 2020;24(10):986-990.

Discovery of an Orally Bioavailable Inhibitor of Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation.

We previously reported the discovery, validation, and structure-activity relationships of a series of piperidinyl ureas that potently inhibit the DCN1-UBE2M interaction. We demonstrated that compound 7 inhibits both the DCN1-UBE2M protein-protein interaction and DCN1-mediated cullin neddylation in biochemical assays and reduces levels of steady-state cullin neddylation in a squamous carcinoma cell line harboring DCN1 amplification. Although compound 7 exhibits good solubility and permeability, it is rapidly metabolized in microsomal models (CLint = 170 mL/min/kg). This work lays out the discovery of an orally bioavailable analogue, NAcM-OPT (67). Compound 67 retains the favorable biochemical and cellular activity of compound 7 but is significantly more stable both in vitro and in vivo. Compound 67 is orally bioavailable, well tolerated in mice, and currently used to study the effects of acute pharmacologic inhibition of the DCN1-UBE2M interaction on the NEDD8/CUL pathway.

Percutaneous catheter drainage followed by endoscopic transluminal drainage/necrosectomy for treatment of infected pancreatic necrosis in early phase of illness.

BACKGROUND AND OBJECTIVES: Infected pancreatic necrosis (IPN) in the early phase is treated with "step up approach" involving initial percutaneous catheter drainage (PCD) followed by necrosectomy. There is a paucity of data on a combined approach of initial PCD followed by endoscopic drainage and necrosectomy. A retrospectively study on safety and efficacy of initial PCD followed by endoscopic transluminal drainage and necrosectomy in IPN. METHODS: Retrospective analysis of data of 23 patients with IPN who were treated with a combined approach. Patients were divided into two groups as follows: patients with central necrosis in whom PCD and endoscopic drainage were done in the same collection (n = 11) and patients with combined central and peripheral necrosis where PCD was placed in peripheral necrosis, and endoscopic drainage was done for central necrosis (n = 12). RESULTS: Endoscopic drainage could be done successfully in all 23 patients with mean time for the resolution being 4.0 ± 0.9 weeks. Fifteen (65.2%) patients were successfully treated using multiple plastic stents while direct endoscopic necrosectomy (DEN) was needed in 8 (34.8%) patients and fully covered self-expanding metal stent was inserted in 6 (26%) patients. The number of endoscopic sessions needed were 3 in 3 (13%), 4 in 9 (39%) patients, 5 in 5 (22%), 6 in 3 (13%), and 7 in 3 (13%) patients, respectively. Patients of central walled-off pancreatic necrosis (WOPN) with PCD catheter in situ needed more endoscopic sessions for resolution as well as more frequently needed DEN in comparison to patients with central WOPN with no PCD catheter. CONCLUSION: The combined approach of initial PCD followed by endoscopic drainage and necrosectomy is safe and effective treatment alternative for patients with IPN.

Frequency & predictors of pancreatitis in symptomatic primary hyperparathyroidism.

BACKGROUND & OBJECTIVES: The frequency and predictors of pancreatitis in primary hyperparathyroidism (PHPT) are not well understood. The objective of the present study was to evaluate the frequency of pancreatitis in patients with PHPT and its association with clinical and biochemical parameters of the disease. METHODS: In this retrospective study all consecutive patients with PHPT registered in the PHPT registry (www.indianphptregistry.com) from the year 2004 to 2013 were included. The clinical, biochemical and radiological parameters related to pancreatitis were evaluated in histologically proven PHPT patients. RESULTS: A total of 218 patients (63 men; mean age: 40.6±14.4 yr) underwent surgery for PHPT during the study. Pancreatitis occurred in 35 [16%, 18 acute and 17 chronic pancreatitis (CP)] patients and male:female ratio was 1:0.94. Skeletal manifestations were seen less frequently in PHPT with pancreatitis as compared to that of PHPT without pancreatitis. PHPT with pancreatitis had significantly higher serum calcium (12.4±2.0 vs. 11.7±1.5 mg/dl, P <0.05) in comparison to PHPT without pancreatitis. PHPT with acute pancreatitis (AP) had higher serum calcium (P <0.05) and parathyroid hormone (PTH) (P <0.05) levels than PHPT with CP. Curative parathyroidectomy improved the symptoms associated with pancreatitis as there was no recurrence in AP group, whereas recurrence was observed only in about 10 per cent patients of the CP group. INTERPRETATION & CONCLUSIONS: Pancreatitis was observed in 16 per cent of PHPT patients with male predominance in the study population. No recurrence of AP was observed after curative surgery. It may be proposed that serum amylase with calcium and PTH should be measured in all patients of PHPT with pain abdomen to rule out pancreatitis.

Fluorodeoxyglucose-positron emission tomography/computed tomography performs better than contrast-enhanced computed tomography for metastasis evaluation in the initial staging of pancreatic adenocarcinoma.

OBJECTIVE: To evaluate the additional role of FDG-PET/CT to the conventional multiphasic CECT in the initial staging of pancreatic adenocarcinoma. METHODS: 54 patients diagnosed with pathologically proven pancreatic malignancy underwent FDG-PET/CECT. The sensitivity, specificity, PPV, NPV, and accuracy of PET/CT and CECT for nodal and metastatic staging were calculated. The statistical difference was calculated by McNemar's test. RESULTS: Of 54 patients, 15 had distal metastasis. The sensitivity, specificity, PPV, NPV, and accuracy of PET/CT and CECT for nodal staging were 33 vs 89%, 84 vs 100%, 67 vs 100%, 60 vs 90%, and 59 vs 95%, respectively, p < 0.001. The sensitivity, specificity, PPV, NPV, and accuracy of CECT for metastatic staging were 73, 87, 69, 89, and 83%, whereas the accuracy of PET/CT was 100%, p = 0.01. By correctly characterizing unsuspected distant lesions, PET/CT could change management in 19% of patients. CONCLUSION: FDG-PET/CT can contribute to change in the management in almost one of every five patients of PA evaluated with the standard investigations during the initial staging.

Blocking an N-terminal acetylation-dependent protein interaction inhibits an E3 ligase.

N-terminal acetylation is an abundant modification influencing protein functions. Because ∼80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a positively charged amine into a hydrophobic handle that mediates protein interactions; hence, this modification may be a druggable target. We report the development of chemical probes targeting the N-terminal acetylation-dependent interaction between an E2 conjugating enzyme (UBE2M or UBC12) and DCN1 (DCUN1D1), a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8. The inhibitors are highly selective with respect to other protein acetyl-amide-binding sites, inhibit NEDD8 ligation in vitro and in cells, and suppress anchorage-independent growth of a cell line with DCN1 amplification. Overall, our data demonstrate that N-terminal acetyl-dependent protein interactions are druggable targets and provide insights into targeting multiprotein E2-E3 ligases.

Prognostic significance of differentiating necrosis from fluid collection on endoscopic ultrasound in patients with presumed isolated extrapancreatic necrosis.

BACKGROUND: Extrapancreatic necrosis is diagnosed on computed tomography (CT) as extrapancreatic changes that are more than fat stranding; both fluid collections and necrosis would have a similar appearance. The aim of this study was to determine the prognostic significance of differentiating peripancreatic necrosis from fluid collection on endoscopic ultrasound (EUS) in patients with presumed isolated extrapancreatic necrosis. METHODS: We carried out a retrospective analysis of prospectively collected data from 36 patients (25 males; age range 19-65 years) with acute pancreatitis (AP) and isolated extrapancreatic necrosis. On EUS, peripancreatic anechoic areas were labeled as peripancreatic fluid collections and peripancreatic heterogeneously echotextured areas as peripancreatic necrosis. RESULTS: The etiology of AP was alcohol in 16 (44.4%) patients, gallstone disease in 13 (36.1%), and other in 7 (19.4%). On EUS, 25 (69.4%) patients had peripancreatic necrosis and 11 (30.6%) patients had peripancreatic fluid collections. Compared with patients who had peripancreatic fluid collections, patients with peripancreatic necrosis had a significantly higher frequency of pleural effusion (88% vs. 55%; P=0.04), organ failure (OF) (68% vs. 27%; P=0.03), and persistent OF (48% vs. 9%; P=0.03). The patients with peripancreatic necrosis also had a higher frequency of ascites (20% vs. 9%), need for intervention (20% vs. nil), surgery (8% vs. nil) and mortality (8% vs. nil), but these differences were not statistically significant. CONCLUSION: Isolated extrapancreatic necrosis on contrast-enhanced CT comprises a heterogeneous group, with patients who show peripancreatic fluid collections on EUS having a less severe disease course compared to patients with peripancreatic necrosis.

Simultaneous Occurrence of Varicella Zoster Virus-Induced Pancreatitis and Hepatitis in a Renal Transplant Recipient: A Case Report and Review of Literature.

INTRODUCTION: Gastrointestinal complications are common after renal transplantation, including oral lesions, esophagitis, gastritis, diarrhea, and colon carcinoma. The differential diagnosis is difficult in this scenario because multiple factors such as drugs, infections, and preexisting gastrointestinal disease come into play. CASE PRESENTATION: We report a case of varicella zoster virus-induced pancreatitis and hepatitis in a renal transplant recipient. The patient underwent renal transplantation 3 years earlier and now presented with severe pain in the epigastrium radiating to his back and had raised serum lipase levels and skin lesions characteristic of varicella. Liver enzyme levels were also elevated. He was started on a regimen of acyclovir. His pain improved in 24 hours, and liver enzyme levels returned to normal in 48 hours. DISCUSSION: There is a paucity of literature on the simultaneous occurrence of varicella zoster virus-induced hepatitis and pancreatitis in both immunocompetent and immunocompromised patients. Our case highlights the gastrointestinal complications of varicella infection in immunocompromised patients that may precede the characteristic dermatologic manifestations, and the fact that rarely both hepatitis and pancreatitis may be seen.

Endoscopic ultrasound guided transmural drainage of walled off pancreatic necrosis using a "step - up" approach: A single centre experience.

BACKGROUND: Walled off necrosis (WON) can be treated endoscopically using multiple transmural plastic stents or fully covered self-expandable metallic stent (FCSEMS) and direct endoscopic necrosectomy (DEN). We evaluated the efficacy of "step-up" endoscopic transmural approach for treatment of WON. METHODS: Retrospective analysis of data of 86 patients with WON who were treated with attempted endoscopic ultrasound (EUS) guided "step up" transmural drainage during last 5 years was done. Initially multiple plastic stents were placed and patients not responding underwent FCSEMS placement and/or DEN. RESULTS: Patients presented 10.8 ± 2.8 weeks after an acute attack of acute pancreatitis and mean size of WON was 10.7 ± 2.9 cm. EUS guided transmural drainage was technically successful in 85/86 (98.8%) patients and 70 (82.4%) were drained with multiple 7/10Fr plastic stents alone while DEN was needed in 9 (10.6%) and FCSEMS was inserted in 6 (7%) patients. All patients had successful outcome with none requiring surgery. The patients who needed DEN/FCSEMS presented earlier and had large size collection with more solid necrotic debris as compared to patients treated with multiple plastic stents alone. The complications were pneumoperitoneum (n = 1), bile leak following cholecystecomy (n = 1), development of external pancreatic fistula following percutaneous drainage (n = 1) and gastrointestinal bleed (n = 1). CONCLUSIONS: "Step up" endoscopic transmural drainage using multiple plastic stents as an initial therapy is safe and effective treatment of WON and avoids more aggressive DEN in majority of patients. Large size WON with more necrotic debris may require DEN.

Capsule endoscopy in small bowel Crohn's disease and Tuberculosis.

Differentiation of small bowel tuberculosis (SBTB) from Crohn's disease (CD) is a diagnostic challenge. We studied 52 patients with suspected SBTB or CD with terminal ileal involvement, who were prospectively enrolled. After confirming patency of the gastrointestinal tract, 26 patients underwent capsule endoscopy (CE). A final diagnosis of CD was found in 18 patients and SBTB in eight patients. All SBTB patients had involvment of the ileocecal valve (ICV) with large (n = 6) and aphthous (n = 2) ulcers in the ileal segment. In CD, ICV involvement was seen in five (33%) patients. Large and aphthous ulcers were observed in seven (47%) and 15 (100%) patients, respectively. On comparison with CD, patients with SBTB had increased frequency of ICV involvement ( P = 0.002) and lesser frequency of aphthous ulcers ( P = 0.007). CE can help in differentiating CD from SBTB by the position of its involvement and the type of ulcers present.